Compositions for peritoneal drug delivery and methods of use thereof

Abstract

Disclosed herein are compositions for administering vaginally of an active agent or a salt to a subject comprising the active agent or salt thereof, a bioadhesive, and an emulsion. Provided herein are methods treating a disease of condition by administering vaginally to a subject a pharmaceutical composition, and kits comprising the pharmaceutical composition. Further provided are methods of localizing an active agent to the peritoneal cavity of a subject while minimizing systemic circulation of the active agent.

What is claimed is: 
     
         1 . A method for treating an endometrial disease or condition in a subject, the method comprising:
 vaginally administering to the subject a polybioadhesive gel comprising:
 (a) danazol or a salt thereof; 
 (b) one or more water-insoluble bioadhesives; 
 (c) at least one oleogel; and 
 (d) at least one aqueous gel, 
   wherein:   the vaginally administering the polybioadhesive gel reduces systemic concentration of the danazol or the salt thereof in the subject by at least 30-fold relative to oral administration of the danazol or the salt thereof to a subject; and   the vaginally administering the polybioadhesive gel localizes the danazol to a peritoneal tissue of the subject, thereby treating the endometrial disease or condition in the subject.   
     
     
         2 . The method of  claim 1 , wherein the vaginally administering is performed once every 24 hours. 
     
     
         3 . The method of  claim 1 , wherein the danazol or the salt thereof is micronized. 
     
     
         4 . The method of  claim 1 , wherein the subject has or is suspected of having infertility. 
     
     
         5 . The method of  claim 1 , wherein the subject has or is suspected of having endometriosis. 
     
     
         6 . The method of  claim 1 , wherein the vaginally administering reduces a number of endometrial lesions in the subject by at least 10% relative to a number of endometrial lesions in the subject before vaginally administering the polybioadhesive gel. 
     
     
         7 . The method of  claim 1 , wherein the vaginally administering reduces a size of one or more endometrial lesions in the subject by at least 10% relative to a size of one or more endometrial lesions prior to vaginally administering the polybioadhesive gel. 
     
     
         8 . The method of  claim 1 , wherein the polybioadhesive gel is formulated as a liquid emulsion. 
     
     
         9 . The method of  claim 1 , wherein the endometrial disease or condition is endometriosis, adenomyosis, or a combination thereof. 
     
     
         10 . The method of  claim 1 , wherein the polybioadhesive gel does not disrupt ovarian function in the subject. 
     
     
         11 . The method of  claim 1 , wherein the vaginally administering the polybioadhesive gel increases a level of the danazol or the salt thereof in the peritoneal tissue of the subject relative to oral administration of the danazol or the salt thereof to a subject. 
     
     
         12 . The method of  claim 1 , wherein upon vaginal administration, the danazol or the salt thereof diffuses into a peritoneal fluid of the subject, reaching further pelvic tissue via transvaginal absorption, thereby localizing the danazol or the salt thereof to the peritoneal tissue. 
     
     
         13 . The method of  claim 1 , wherein the subject is administered the polybioadhesive gel daily for 5 to 7 consecutive days. 
     
     
         14 . The method of  claim 1 , wherein the danazol or the salt thereof is administered at a dose of 100 mg. 
     
     
         15 . The method of  claim 1 , wherein the danazol or the salt thereof is administered at a dose of 200 mg three times daily for 5 to 7 consecutive days. 
     
     
         16 . A method of maintaining ovarian function and reducing pain associated with endometriosis in a subject, the method comprising:
 vaginally administering to the subject a polybioadhesive gel comprising:
 (a) an active agent or a salt thereof; 
 (b) one or more water-insoluble bioadhesives; 
 (c) at least one oleogel; and 
 (d) at least one aqueous gel, thereby maintaining ovarian function and reducing pain associated with endometriosis in the subject, 
   wherein:   the vaginally administering the polybioadhesive gel reduces systemic concentration of the active agent or the salt thereof in the subject by at least 30-fold relative to oral administration of the active agent or the salt thereof to a subject;   the active agent or the salt thereof diffuses into a peritoneal fluid of the subject, reaching further pelvic tissue via transvaginal absorption, thereby localizing the active agent to the peritoneal tissue.